Adapt Czochralski to Chiral Separation

[Enthalpy]

Hello dear friends!

Some "chiral" molecules have a right and a left form.
http://en.wikipedia.org/wiki/Chiral_resolution
http://iupac.org/publications/pac/69/7/1469/pdf/
Biology demands pure enantiomers, especially for drugs, but identical chemical properties make this difficult.

Most racemates mix tightly the enantiomers one-to-one when they crystallize, but a few ones separate spontaneously into right and left crystals. To my understanding, such a purified carboxylic acid can separate chiral amines by making salt crystals of differing properties - and purified amines can separate chiral acids. Or such a substance can serve in a chromatography column to separate a produced racemate.

Could chiral solvents be useful? I haven't read about them. I imagine they could dissolve a racemate and, as they evaporate, let one enantiomer crystallize first and the other later.

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For substances that separate spontaneously, a historical separation process puts two enantiomorph distant crystal seeds in a solution to better control the separation in two forms.

One could make a quick machine that concentrates light on little more than the crystal's size, so the optical rotation effect is very perceivable, and analyze only deflected light, which then comes necessarily through the crystal. Optionally, sort the crystals by size first, say by upwind. Use several rays to avoid the bad crystal axis. Sorting machines have often an air jet to spew away the desired items. An air valve reacts in ~20ms, the rest of the circuit must be optimized.

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The very controlled Czochralski's process grows huge, nearly-perfect single crystals of semiconductors.
http://en.wikipedia.org/wiki/Czochralski_process
It has a liquid bath of the material, under slightly melting conditions, and one single zone under slightly solidifying conditions (colder) where a single crystal is already present (at the beginning, it's a seed cut from a previous crystal), so the solid grows only at that crystal, reproducing its organization, orientation...

Semiconductors crystals are grown very slowly to have very few dislocation. Because of the crystal's perfection, and because impurities have time to dissolve again, silicon purity passes from 1ppm in the melt to 0.1ppb in the crystal.

I suggest to adapt it to chiral separation. Organic compounds can be dissolved instead of molten; the local under- or over-saturation could result from temperature too.

 

 

Harvesting both enantiomers keeps the solution racemic. Jaws can hold the growing boule once the diameter is attained.

• The huge selectivity resulting from controlled growth is advantageous.
• The choice of the seeds determines the crystalline form, for instance the most stable. Nice at polymorph substances.
• Maybe some final products that normally mix R and S molecules in their crystals would also grow only-S and only-R crystal forms, under such good conditions? This would save the amide step.

Czochraslki could crystallize with high selectively more compounds beyond racemates, for instance the amide obtained from a pure enantiomeric amine with an acid.

Marc Schaefer, aka Enthalpy

[hypervalent_iodine]

Hello dear friends!

 

Some "chiral" molecules have a right and a left form.

http://en.wikipedia.org/wiki/Chiral_resolution

http://iupac.org/publications/pac/69/7/1469/pdf/

Biology demands pure enantiomers, especially for drugs, but identical chemical properties make this difficult.

 

Most racemates mix tightly the enantiomers one-to-one when they crystallize, but a few ones separate spontaneously into right and left crystals. To my understanding, such a purified carboxylic acid can separate chiral amines by making salt crystals of differing properties - and purified amines can separate chiral acids. Or such a substance can serve in a chromatography column to separate a produced racemate.

 

Could chiral solvents be useful? I haven't read about them. I imagine they could dissolve a racemate and, as they evaporate, let one enantiomer crystallize first and the other later.

 

----------

 

For substances that separate spontaneously, a historical separation process puts two enantiomorph distant crystal seeds in a solution to better control the separation in two forms.

 

One could make a quick machine that concentrates light on little more than the crystal's size, so the optical rotation effect is very perceivable, and analyze only deflected light, which then comes necessarily through the crystal. Optionally, sort the crystals by size first, say by upwind. Use several rays to avoid the bad crystal axis. Sorting machines have often an air jet to spew away the desired items. An air valve reacts in ~20ms, the rest of the circuit must be optimized.

 

----------

 

The very controlled Czochralski's process grows huge, nearly-perfect single crystals of semiconductors.

http://en.wikipedia.org/wiki/Czochralski_process

It has a liquid bath of the material, under slightly melting conditions, and one single zone under slightly solidifying conditions (colder) where a single crystal is already present (at the beginning, it's a seed cut from a previous crystal), so the solid grows only at that crystal, reproducing its organization, orientation...

 

Semiconductors crystals are grown very slowly to have very few dislocation. Because of the crystal's perfection, and because impurities have time to dissolve again, silicon purity passes from 1ppm in the melt to 0.1ppb in the crystal.

 

I suggest to adapt it to chiral separation. Organic compounds can be dissolved instead of molten; the local under- or over-saturation could result from temperature too.

 

ChiralSeparationCzochralski.png

 

Harvesting both enantiomers keeps the solution racemic. Jaws can hold the growing boule once the diameter is attained.

• The huge selectivity resulting from controlled growth is advantageous.
• The choice of the seeds determines the crystalline form, for instance the most stable. Nice at polymorph substances.
• Maybe some final products that normally mix R and S molecules in their crystals would also grow only-S and only-R crystal forms, under such good conditions? This would save the amide step.

Czochraslki could crystallize with high selectively more compounds beyond racemates, for instance the amide obtained from a pure enantiomeric amine with an acid.

 

Marc Schaefer, aka Enthalpy

 

Chiral solvents have been shown to be useful when trying to promote the formation of one enantiomer over another during a reaction, but I have not seen them used in the way you describe. The main draw back is that they are expensive and solvents are required in large volumes.

 

Separation by crystallization is interesting and admittedly not something I know terribly much about. Practically speaking, separation of chiral compounds in organic chemistry is usually achieved in other ways, such as kinetic resolution.

 

One problem I see with your device is with solvent. Many organic compounds will not dissolve in water and would typically be recrystallized from any number of volatile, flammable and/or toxic organic solvents. At the same time, some organic compounds have high melting points - certainly higher than the boiling point of the solvent(s) they're in.

 

It also strikes me that this would be limited in its scope in an organic lab, though it's possible that it would find use in other areas.

[John Cuthber]

Not all chemicals can be melted.

Not all chiral mixtures crystallize out as single isomers.

The classic example- resolution of sodium ammonium tartrate by Pasteur only works at low temperatures- if the energy is high enough to essentially break all the bonds between molecules (i.e. to melt it) then the interactions that distinguish racemic crystals from individual isomers will be much smaller than the typical energy and so the separation won't work.

 

It might work in a rather small number of cases.

On the other hand, this

http://en.wikipedia.org/wiki/Chiral_column_chromatography

works quite well.

[Enthalpy]

Thanks for your interest!

 

If Czochralski permits to produce chiral solvents for cheaper, it may spread their use.

 

Crystallization would be made either from a melt (improbable, as many organic compounds decompose before) or from a solution. All processes use a solvent, Czochralski is just a far better controlled process.

 

Only for organics, or even only drugs, which are the essential reason for chiral purity. If Czochralski can produce pure enantiomers of a few standard acids and amines, which in turn permit to screen drugs, I'll be satisfied.

 

I want to use standard crystallization temperatures. Maybe the link from silicon to organics wasn't clear enough. Silicon is crystallized from the molten element, but organics should crystallize rather from a solution at a reasonable temperature.

 

And, yes, only a few compounds are known to separate spontaneously into left and right (I suppose the isomers are separated in a previous step usually). To my understanding, these exceptional compounds serve to screen others, for instance:

a pure left amine makes with a racemate acid two amides with different crystallization properties, because the two amides are isomers but not enantiomers.

Hence the usefulness of having these special compounds abundent, pure and cheap.