New ways to quench

Ground Up Think Tank
1

Ok so ,

While working on a new sop s

For isomerizations from cbd> thc I started to realize that the route most of us take in the quench is tedious, and giving a lot of losses to the water of product and there must be better ways

So we quench a reaction to stop it from proceeding that’s obvious but at the same time we are doing this we are most likely making a product with

Lower yield in %

Lower yield in volume

And creating a massive amount of waste so this got me thinking can it be done different ?

Answer is very likely YES

Now all we need to figure out is how

I ll take the aluminiumcloride on dcm sop as an example

So we quench the reaction with water / potasium sulfate

We are dumping this proton soup straight into our reaction mixture to stop the reaction and as a result a lot of questions come to mind

Is there right when the water hits the dcm reaction a rxn happening that takes some of our yield to thc D8 ?

We know that dcm and water do not mix ( not miscible)

So mixing speed is the quenching reaction speed

We know that if the aluminium has no where to go to it will make aluminium oxide Wich in turn will give horrible emulsions

And we know that this quench on it s own is not sufficient to take all aluminium out of the reaction and that further cleanup is needed (naoh) wash and even activated carbon scrub

At the same time these washes take time

These washes leache product

These washes generate waste etc etc

So the idea is to find quenches that are less in all of the above Wich takes me to solids or solid supports

Now since our solvent in this example is DCM there are a lot of solid supports that will not work for the solvent will attack them and make them swell at best or dissolve them at worse.

So we need to use reagents that can withstand the aggressive nature of the solvent.

In this example where anhydrous alcl3 is added to dcm a simple filtration will take 80% of your alcl3 from the reaction
As will a filtration run on your ptsa/hexane solution

First that come to mind are salts dcm does not dissolve a lot of salts so I would imagine that passing the reaction tincture treu a crc stack of salts that have a aluminium affinity could work

But I also think in the realm of

Loaded molecular sieves

Passing the tincture over a bed ( crc stack) of molecular sieves might work

The amounts of reagentia that needs to be taken care of is minimal

And the fact that we are willing to trow x fold of liters off water at it is fairly stupid

Knowing that the water robs

Us of good product and time

And Leaves us with a load off waste

So the question is how should we quench our reactions better ?

Wich reagents would be the best option to use ?
The most used reagents in isomerizations are
Ptsa
Alcl3
Borontriflouride
Triisobutylaluminium

It should not be to hard to find good solid quenches for these 4 Lewis acids

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Contemplating on solutions the following comes to mind
Trow a base that has no water in the reaction vessel for the main quench
Like a amine (analine example for alcl3)
Then pass treu a accitic or basic solid medium to catch reagents
Salts
Bentonite clays
Molecular sieves ( loaded example sapo 37)
Silica solid supports
Loaded activated carbon supports
For sop s where alkanes are the solvent of choose polystyrene beads could be implemented

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Why not quench in line? Take a feed from reaction vessel, attach it to a tee and take another feed from ur quench/basic solution and mix them on demand.
Send that thru a molsieve at the end and then filter stacks. Youll get maximum molecule exchange by doing it in small 5ml increments continously, instead of using 5L to quench a big bulk batch at once which requires lots of mixing speed and agitation.
You could even have it done in two stages, after it goes thru the above processes, attach that feed to another tee and plumb in another milder quench solution, to finsish it off. It should be dried down between stages from the molsieves.

The beauty to all of this is minimal hose movements which equates to less oxygen and more inert environments.
You only open the vessel to start the reaction and anything being injected in can be pre-dried and backfilled with argon in a bottle or bucket or keg depending on scale

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Similar to my thoughts, but with a solution that wouldn’t be water which is virtually impossible besides glycerol, and I don’t feel good about that, so in-line column with fins for agitation and a column directly after filled with sieve and carbon and then another column following with a stack setup for any residing metals and correction purposes if this were the route.

So in turn would make water a better possibility with the base of choice for quench.

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This works BUT either way is still a waste heavy method
I am yust starting with writing options
But since alcl3 as example has so many refrances I think that something like a cold same temp or lower than reaction vessel crc stack of anhydrous potasium sulfate
Where the reaction is injected treu might do the trick already
Making potasium/aluminium sulfate

6

Sodium hydroxide dissolves in dcm
So that could also work keeping it 1 solvent based

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7

How about ammonia gas ? Gotspe check for solubility in solvents thou

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Sodium hydroxide completely dissociates in water as long as your ph isnt too high so technically it would be Sodium ions and hydroxide ions

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I did read about gas to stop the reaction as well but wasn’t to sure about the efficiency

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Yes but the aim is to find quenching methods that use no water (proton soup) only solids
Preferably regenerating solids
And get to 0 ppm of reagents

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I will be working on a quenching method this week actually. I have been contemplating it for a while, and should hopefully have the required materials this week! I too believe that in-line is the way to go. I’m actively trying to restructure my lab to be as in-line as possible.

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Great hit me up I have some questions and your dm is out

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I feel it always can be said: you sir are fucking insane and I respect that. If you were anyone else, I wouldn’t even say these chemicals. No one here should try this; not even me lol.

These are tricky things to work with; DCM loves to form emulsions, I avoid it like the plague for toxicity alone, but it’s rough to deal with in LLE. Perhaps after quenching, you could boil off your DCM to make your cleanup easier (just use vacuum and no heat).

Adding a non-protic base. This is a hard line to walk. Something like n-butyl lithium would be pretty extreme and could cause side reactions even if you cool to dry ice temps, though you would just be left with lithium salts and butane. Sodium methoxide/ethoxide/isoprpoxide could walk this line if you’re a lower temperature which you may need just to deal with heat generated by the quench. Youd need to dry the shit out of your glass, distill the alcohol over sodium to remove hydroxides, then make your alcohol hydroxide, but you would be proton free more or less (I’d recommend isopropanol to minimize proton donorship).

Of course, anywhere in-between is fair game, lithium/sodium/potassium hydride, lithium/sodium amide can work too, hydrides may be the way to go IMO.

If you’re ok with some protons in the mix, dry ammonia might be a good choice if you want something more mild. Not sure how that will react with BF3 or TIBA, (likely angrily) but it could get the job done and would maintain anhydrous conditions.

Perhaps an exchange resin could meet your needs. Since they operate on an equilibrium, you can load it with whatever you like, but it could come back to bite you since you may not be able to fully neutralize. The solvents your using may dissolve the beads as well.

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:joy::joy::joy::joy: let me catch some breath and get back to you

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15

Have you tried to break the emulsion with a centrifuge?

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If you can take out 80% of AlCl3 after the reaction by filtration
and NaOH is soluble in DCM
why not just filter, then add 0.2-0.25 eq NaOH (more if necessary) to force the AlCl3 → Al(OH)3 equilibrium to the right
for the record I think KOH is much more soluble in DCM, especially when powdered
then filter out the Al(OH)3 salts. Boom, non aqueous quench

(to be safe, I would still do a biphasic extraction and hit the DCM layer with saturated NaHCO3 to neutralize pH afterwards and pull the trace aluminum salts out of the organic layer)

I’m assuming you’ve tried this already though

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Could all the polar baddies be removed by filtering with the right amount of silica, or by “pulling a plug”?

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This is where so far activated carbon is superior ( waste water cleaning principal)

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Polar is not the isseu charged is
Reason my hunt is on a charged counter solid if we are able to quench crc style scaling becomes much easier

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Isn’t that even more polar and sticks favourably to the silica compared to the target compound?

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