derivatisation of formate (any carboxylate)

[Tremenda]

I have come to realise that in order for a derivatisation on a carboxylic acid to take place, it needs to be protonated. The hydrogen is important in the mechanism.

The sodium formate is pretty much insoluble in everything except water and alcohols (According to the literature, unless you could enlighten me with an aprotic solvent that does the job).

Therefore, I want to acidify an aprotic organic solvent in which formate is insoluble and, as formic, add the derivatising agent. Formic acid seems to be soluble in everything

There are very few non-aqueous inorganic acids that are reasonably safe to handle. A simple one I can come up with is 100% sulfuric acid.

My question is: will the derivatising agent react with the sulfuric acid if I add the acid to the organic solvent containing the insoluble formate?

Regards

[krickos]

Ji

If I understand you correctly, you are looking for an carbo acid in sodium fumarate.

You may not need a reaction solvent to complete the analysis. For instance there is a "direct" derivatisation method of sodium stearyl fumarate in the europen pharmacopiea. In short it goes like this:

Sample solution
Weigh 15 – 25 mg of sample into a GC-vial with a screw cap. Add one ampoule (approx. 1 ml) of silylation reagent (BSTFA + 1 % TMCS, silylation reagent in 1 ml glass ampoule ).

Treat reference- and sample solution as follows:
Seal the vials immediately with a teflon faced silicon septum and aluminium cap and heat at 70 °C for 1 hour. After the reaction, a precipitate remains in the vial. Filter the solutions through a suitable 0.45 µm nylon filter into another GC-vial. Seal the vials. Inject on GC.

BSTFA+TMCS has good solvent properities and can function without additional solvents. If your samples do not dissolve even at elevated temperatures you might consider using dry DMF or DMSO as sample solvent.

[Tremenda]

Hi,

According to the recipe, I just need to add the derivatising agent and heat?

No solvent needed, nor addition of acid?

I have tried that at room temperature but it did not work.
I will try increasing the temperature and I will post the results.

Thanks

[HW Mueller]

Am I getting abridged contributions now? I didn´t see any question about fumaric acid (a dicarboxylic unsaturated acid with 4 C), formic acid has one C.
Also, what is a carbo acid in Na fumarate?

Tremenda, maybe your derivatization compounds need the acid, but that is not generally true, the carboxylate can also react.
Just about any chemical can be handled safely if you know what you are doing, 100% H2SO4 certainly needs special attention. Also, if you add that to an organic solvent you may get a mess.
I just wonder how many times your problem has been solved before.

[Tremenda]

Hi,


I thought it would be easier.
I am also wondering the same. It should be something many people working with derivatising agents for GC must know...

Hopefully they will read this thread...

Thanks for your reply

[krickos]

Well

Apologies for the confusion. However the example I gave should still valid.

In D.R. Knapps handbook for analytical dervatization reactions there is a similar example for carboxylic acids/sodium salt, where BSA:TMCS 9:1 is used and the reaction was completed in room temperature after 30mins.

BSTFA is quite like BSA with exception of replacing some H for F, which usually gives faster and more complete reactions. The addition of TMCS will increase the reactivity of the reagent and also help if you got steriacally hindered targets, ratio is typically in range of 99:1-5:1.

If you got a di-acid you obviously tend to get a double dervatization and one have to make sure that you add enough reagent.

Tremenda, you stated that you have tried something before at room temperature but excatly what reagent?

And yes, in best case one can avoid any solvents or other additives (increases risk of traces of water that can interfer with reaction).

Also, what is a carbo acid in Na fumarate?

Well was uncertain if Tremenda was looking for traces of carboxylic acids in the salt or "just" was trying dervatization on the salt.

[Tremenda]

Thanks for your reply.

I want to derivatise traces of sodium formate. However, I wanted to carry out first a simple test on a respectable amount of sodium formate and it did not work.

I am using MBDSTFA. The TBDMS-carboxylates are more stable and less prone to hydrolisation than TMS-carboxylates.

This is meant to work as it is according to the leaflet that comes with it, with no extra additives.

It could be that I could add a small amount of an activator. But I don't know which one.

Have you used this silylating agent before?

Regards

[krickos]

Hi

Agreed those derivatives are more stable than TMS-derivatives.

I have worked with a similar reagent MTBSTFA to analyse smaller amounts of an carboxylic acid in an organic substance. In that particular case due to the molecules at hand we had to dissolve sample in dry toluene, add some pyridine as catalyst and add reagent and heat treat.

If my references are correct I belive it is both true for MTBSTFA and MBDSTFA that they may react at room temperature with amines but for hydroxyls you need to heat treat, like 60-70°C for 30-60mins. Please note that I did not find any reference for those two for the salt form of the acid so unsure if these reagents will work on your sample.
So as you stated earlier just try heating sample+reagent first and see if you get suceesful before starting to use additives/solvents or changing reagent.

An economical point as well: If you gonna do this analysis routinly you might want to consider trying BSTFA:TMCS even if you get MBDSTFA to work. BSTFA:TMCS was 4 times cheaper than MBDSTFA/MTBSTFA reagents last time i looked it up. Especially if you are going to work with pure samples that can be dried/moist protected to minimise risk of hydrolysis.

[Tremenda]

Hi,

I prepared a simple experiment consisting of an excess of sodium formate (solid) and an excess of MBDSTFA.

By using mild conditions, i.e. 70ºC 1 hour, I got a small peak of TBDMS-formate. By increasing time it only improved by 20%.

I went to tougher conditions such as 150ºC (Boiling point of MBDSTFA is 170 ºC) for 1 hour to see an increase of 300%. By longer time at this temperature I see increments of 20% per hour.

2 problems with this:
The conditions are too extreme. Formic might decompose.
The peak is tiny (comparable to other impurities found in the MBDSTFA) and it proves extremely hard to derivatise.

These conditions are of no use for small amounts of formic acid.

The only thing I could do now is liquid-liquid extraction.

I will post the results.

Thanks