Problems purifying

Hi! My name is Marta and I am a Spanish Chemistry student. I am having problems in the laboratory purifying a compound and I would be grateful if you could help me.
I have carried the protection of one of the aldehyde groups of the terefaldehyde with ethylene glycol 1:1. I have had a lot of problems trying to purify it. I always get a mixture of my product and the tereftaldehyde. I have used a cromatography column and 1:1 hexane / DCM as eluyent.
I would appreciate it if you could recomend me a new way to purify it or maybe a change in what I have done.

Thanks in advance!

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Reply 1

EierVonSatan

You're getting a mixture of the dialdehyde and the monoprotected product? If there's only a small amount of starting material present (say 1:10) you may be able to recrystallise it using an appropriate solvent/anti-solvent. If it's a more substantial mixture, I'd suggest using a few different solvent systems and testing them on a tlc plate (such as hexane/diethy ether or hexane/ethyl acetate) to see if you can get better separation - a taller column may help if separation remains poor (and you should be doing this under pressure, if you're not already),

Another thing to consider is how far the reaction has proceeded before you purify the reaction - i.e. could your product be degrading on the column? Or is starting material still present after you've stopped the reaction? I ask because you have an acid sensitive product and silica columns are slightly acidic.

(I'll assume that this is a first step in large scale thus not practical for HPLC and the like)

(edited 10 years ago)

Reply 2

Midlander

Original post by Marta Magia

Acetonide protections are very temperamental because even a little bit of residual acid can take the group off which makes standard column chromatography unsuitable. Check around your lab for acid scavenger resins (NH2 adsorbent columns), which will get rid of any free acid from your reaction and make purification much simpler.

Reply 3

illusionz

Original post by Midlander

Or can't you just add a bit of ammonia solution to the eluent? That's what I've always done.

Reply 4

EierVonSatan

Original post by illusionz

Or can't you just add a bit of ammonia solution to the eluent? That's what I've always done.

You can, or triethylamine as I do, but it's just not as fancy sounding.

Reply 5

Midlander

Original post by illusionz

Or can't you just add a bit of ammonia solution to the eluent? That's what I've always done.

I suppose so but the base-adsorbed columns I used for this reaction a few years ago worked wonders. More than one way to skin a cat :smile:

Reply 6

charco

Study Forum Helper

Original post by Midlander

I suppose so but the base-adsorbed columns I used for this reaction a few years ago worked wonders. More than one way to skin a cat :smile:

[no animals were hurt or distressed in the making of this post]

Reply 7

Marta Magia

Original post by EierVonSatan

Yes, I'm getting a mixture of the dialdehyde and the monoprotected product, and there also is some of diprotected so that's why I always have dialdehyde in the reaction.

The monoprotected product is an oil at room temperature, so I can't recrystallise it, or can I? The dialdehyde is solid... could I recrystallise it the other way round? I mean... I recrystallise the dialdehyde, then get rid of it and remove the solvent from the remaining liquid? Now that I say it, that wouldn't be rigours...

Yes, probably the product degrades in the column so the column was "desactivated" with a solution of 5% NaHCO3 and then dried in a heater. Sorry, I forgot to say that. The columns haven't been done under preassure because they do not separate. The fractions are all impure in that way. I have also tried a column where I have 20grams of "desactivated" silica for every 1gram of product and I still get impure fractions.

Your assumption is correct, this is the first step of all.

Thanks a lot for your advice and you have giving me something to think about with "You can, or triethylamine as I do, but it's just not as fancy sounding"

Reply 8

Marta Magia

Original post by Midlander

I suppose so but the base-adsorbed columns I used for this reaction a few years ago worked wonders. More than one way to skin a cat :smile:

Do you mean to "desactivate" the silica? for example with a solution of 5% NaHCO3 and then dried in a heater? That's how the columns were done... but still wasn't good enough

Reply 9

Midlander

Original post by Marta Magia

Do you mean to "desactivate" the silica? for example with a solution of 5% NaHCO3 and then dried in a heater? That's how the columns were done... but still wasn't good enough

No, I mean columns with acid scavenging resins adsorbed to the silica.

Reply 10

EierVonSatan

Original post by Marta Magia

I didn't think that it would be a liquid :p:

You can still recrystallise it, but only if it's a solid at a low temperature you can replicate in the lab, say at 0^oC but it can be a bit more fiddly. That said it seems like you've got a non-insignificant amount of impurity so this probably won't help you.

Yes, probably the product degrades in the column so the column was "desactivated" with a solution of 5% NaHCO3 and then dried in a heater. Sorry, I forgot to say that. The columns haven't been done under preassure because they do not separate. The fractions are all impure in that way. I have also tried a column where I have 20grams of "desactivated" silica for every 1gram of product and I still get impure fractions.

Not to worry, it's difficult to cover everything :smile:

A 20:1 ratio is about normal for an easy-moderate separation (with good silica), you might want to try 50:1, though on a large scale I understand that this becomes very laborious, very quickly.

Gravity columns are rubbish. A flash column is much more effective for separations, particularly for troublesome cases, and by pressure I don't mean high pressure - just the kind from an in-house air flow system or manual pump :yep:

Your assumption is correct, this is the first step of all.

Thanks a lot for your advice and you have giving me something to think about with "You can, or triethylamine as I do, but it's just not as fancy sounding"

Yes, this is another way to deactivate the silica, you use a 1% triethylamine solution of your eluent, but be careful to adjust your mixture before hand, as it will often change how fast the compounds will move on the column. It also makes tlc plates streaky.

Since the M_r of the compound isn't too high, a reduced pressure distillation may be another option. I tend to prefer distillations over columns, personally :ninja:

It's effectiveness will depend on the boiling point difference between the two, but it may clean it up enough so that a column separate afterwards becomes much more fruitful.

Good luck :p:

(edited 10 years ago)

Reply 11

Marta Magia

Original post by Midlander

No, I mean columns with acid scavenging resins adsorbed to the silica.

I've never heard of that, so thanks a lot! I will ask and study it!

Reply 12

Marta Magia

Original post by EierVonSatan

I didn't think that it would be a liquid :p:

(...)

Good luck :p:

wow! you've really giving me a lot of information. I'll study all of them with the people in my lab and see what we can do.

THANKS A LOT FOR ALL THE HELP! :biggrin:

Reply 13

Midlander

Original post by Marta Magia

I've never heard of that, so thanks a lot! I will ask and study it!

Not a problem-the issue I would have with washing the column with base is that I presume you run into issues with solvent miscibility from the aqueous wash.