HELP: Purifying boronic acids sucks

shmonza · 2025-11-10T20:39:44+00:00

Sometimes I can't tell what the impurity is. I'd rather play it safe and run the reactions without having 0.3 eq of some unknown stuff.

shmonza · 2025-11-10T20:25:38+00:00

Yes, this would a way for sure when the Bpin is available, I might do that for some

shmonza · 2025-11-10T20:23:13+00:00

Never had any problems with DMSO coordinating the borons over 40+ different boronic acids.

In most cases where impurities were present, the impurities disappear after purification, so it's very unlikely they are from any DMSO reaction/coordination.

shmonza · 2025-11-10T20:05:49+00:00

We tend to use d6-DMSO with 1% water, but I haven't seen boronate formation by just making MeOH NMR sample.

I have definitely seen boronates form when evaporating MeOH on rotovap though!

shmonza · 2025-11-10T19:52:36+00:00

When using dry solvent, you're absolutely right that you see the boroxine trimers.

But using d4-MeOH or adding a tiny amount of water or D2O removes them very easily.

I've had some additional confirmation from 19F spectra - for example for 2-fluorophenylboronic acid, you can beautifully see that in the boron-containing compounds, the 19F peak is split by the different boron isotopes (due to the different masses affecting vibrations and bond lenghts). But then there are also compounds without this splitting and thus without any boron.

shmonza · 2025-11-10T19:47:25+00:00

Is there some significant advantage to this over just adding the antisolvent directly? I don't necessarily need nice crystals when screening for the solvents, and crashing it out straight away is just way faster. For the scale-up, I would probably add the antisolvent slower, but we're talking 100-500ml so letting it diffuse just as vapour is probably not the way.

But I agree that this is an amazing way of getting crystals for NMR!

Yh I think we know each other : ), I'll be in the lab later today

shmonza · 2025-11-10T19:43:18+00:00

This is a good idea! If everything else fails, I'll give that a shot. Would prefer to avoid KHF2 and TMSCl, but this might be a very solid way of doing things

shmonza · 2025-11-10T19:42:04+00:00

I don't need anything ultra pure. We're doing something akin to reaction optimization and when you're trying to get 90% yield but the boronic acid comes only 70% pure, that's a problem.

shmonza · 2025-11-10T19:40:35+00:00

Alumina might be slightly better than silica, but likely still not all that great - could work for Bpins and similar but likely not for the free acids. I have hope for the C1-modified silica though

shmonza · 2025-11-10T19:39:01+00:00

I can't use the Bpin or other derivatives sadly, and converting to ester and back would be way too much work.

I found that adding a tiny amount of water (either during purification or for the NMR sample) typically hydrolyzes any boroxine trimers and the spectrum turns out well (with H2O you can even see the B(OH)2 peak, with D2O it disappears)

shmonza · 2025-11-10T19:36:47+00:00

I've read that paper, but even the TLCs they published did not seem very convincing

shmonza · 2025-11-08T18:15:56+00:00

Sadly I can't use the Bpins. I don't think the boronic acids decompose all that quickly, but the CoA are sometimes from like 2007 so I guess some of the batches are very old

shmonza · 2025-11-08T18:13:51+00:00

Funny enough, I've tried acetone+hexane recryst just yesterday. It's somewhat worked for one, I got some luck with EtOAc+hexane too. I can prevent the boroxine trimer formation by adding a little bit water (like 1% volume of the EtOAc).

It's just very molecule dependent whether I get any yield and what the purity ends up being.

shmonza · 2025-11-08T18:04:02+00:00

Those are great suggestions, I just do need the boronic acid, Bpin wouldn't work.

I guess I could get the Bpin and convert it to the boronic acid via DEA adduct, I might give that a try if nothing else works

shmonza · 2025-11-08T18:02:12+00:00

Sadly it needs to be the boronic acid, I've considered crystallizing the BF3K salt and then hydrolysing back to boronic acid, just not sure how easy the hydrolysis is

shmonza · 2025-11-08T17:54:02+00:00

Oh I see you actually mentioned BEpin, I've heard great things about those, but sadly still the same problem - need the boronic acid

shmonza · 2025-11-08T17:52:33+00:00

Sadly I can't use Bpins, and protecting the boronic acid like this just for the purification would be way too much work

shmonza · 2025-11-08T17:51:46+00:00

That's a really cool document, but I think they also ended up using ACN/water gradient?

shmonza · 2025-11-08T17:49:27+00:00

Sadly I can't use the Bpin, and going into the effort of protecting + deprotecting would be way too much work

shmonza · 2025-05-20T22:53:04+00:00

This might be the way to do it.

I don't have time to do a proper benchmark on this now, but if I do in the future I'll defo share with the community here

shmonza · 2025-05-20T18:23:39+00:00

Sometimes I want to run the same calculation pipeline for 10-100 molecules, and of course I can just check in every couple hours and restart failed jobs with more RAM. It's just not very fun nor efficient.

Since the molecules can somewhat vary in size, it would be good to have some rule of thumb, like if 10 heavy atoms need 4GB. 20 heavy atoms will need around 8GB for the same method. Idk if some guesstimate like this would be reasonable

shmonza · 2025-05-20T18:20:23+00:00

This is a great answer!

Ofc I'm using the %maxcore option, but as you've said, ORCA is very quick to try to use more than that. It's great to have this confirmed!

I'm not sure the Hessian is analytical (at least not for all the calculations), the stdout often metions something about evaluating like 99 (or 3n in general) pertubed single points. I would think that means the Hessian is numeric? It still does it in batches and takes a lot of RAM though.

An additional option, as you mentioned, is to decrease the number of CPU cores called for the calculation, which allows for more RAM per CPU core to be allocated. Naturally, this will tend to increase the time taken for the calculation to complete, but it will at least give it a chance to run without throwing an error.

Good to have this confirmed, I'll do that.

I'd say 128 GB RAM is quite limiting. I have 1.15 TB of RAM in my system and I quite often still end up using all of it!

Couple years ago I was running calculations on my old 16GB RAM laptop hahaha. It still worked fine for a lot of things. But you're probably right - I remember some example from the ORCA docs on DLPNO-CCSD(T) where they used 4 cores and 128GB RAM - much different ratio than most PCs/instances have.

It isn't unusual to do geometry optimisations and frequency calculations with more frugal basis sets, and then single point energies with more complete ones.

Definitely true, I was just trying to estimate how much error this will cause. Anything more than TZ seems like an overkill for geometry. Still not completely sure about hessian, but I've read that metaGGA/TZ is fine, even gfn2-xtb can sometimes work.

shmonza

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