[Greig]

Hi,

I am a new PhD student who does not at all specialise in organic chemistry but there is a particular compound I would like to synthesise.

The molecule is terephthalic acid with one sulphonic acid group.

The formula would therefore be C8H6SO7.

My first attempt was the direct sulphonation of terephthalic acid using conc. Sulphuric acid. The problem was that the product formed was actually the dimer anhydride of terephthalic acid with one sulphonic acid group (the acid also catalysed the formation of anhydride).

I also tried the oxidation of p-xylene sulphonic acid using acidified potassium permanganate but no precipitate was formed and extraction of a sulphonic acid from sulphuric acid and chromate I figured would be very complicated.

I have found myself leaning towards the protection of terephthalic acid by forming the methyl ester on both acid groups. Then I will attempt to sulphonate this and saponify the ester.

I foresee that even if I form the desired compound it may be very difficult to extract from the excess sulphuric acid used as reactant.

Does anyone have any suggestions for extracting such fairly similar compounds?

Any other insight on how best to do the reaction would also be much appreciated. I have found absolutely no literature on this fairly simple compound and I am beginning to think there's a reason for that!

Thanks,

Greig

[Honclbrif]

"My first attempt was the direct sulphonation of terephthalic acid using conc. Sulphuric acid. The problem was that the product formed was actually the dimer anhydride of terephthalic acid with one sulphonic acid group (the acid also catalysed the formation of anhydride)."

If you got the the properly sulfated anhydride dimer, could you not simply hydrolyze the anhydride? 1N NaOH should go through that like a flaming sword. If you use the methyl ester you can also probably avoid your dimerization problem as well.

As for the KMnO₄ route, I picked this reference up off of Reaxys

A supramolecular nematic phase in sulfonated polyaramides
Sebastien Viale ,  Adam S. Best ,  Eduardo Mendes ,  Wolter F. Jager and Stephen J. Picken
Chem. Commun., 2004, 1596-1597

DOI: 10.1039/B404809C

http://pubs.rsc.org/en/Content/ArticleLanding/2004/CC/b404809c

As an absolute last resort, you can get 2-Bromoterephthalic acid from Sigma. You may be able to induce a nucleophilic aromatic substitution with sulfite via a Strecker sulfonate synthesis, or add a thiol with H₂S for a possibly cleaner oxidation route.

[Greig]

Thank you very much for a very helpful response! The reference is exactly what I need. Reaxys seems like a great source, pity I don't have access.

Regarding your question:

"If you got the the properly sulfated anhydride dimer, could you not simply hydrolyze the anhydride? 1N NaOH should go through that like a flaming sword. If you use the methyl ester you can also probably avoid your dimerization problem as well."

I thought of this but the problem is that only one of the two aromatic rings in the dimer is sulphonated, so I would get a (hard to separate?) mixture of terephthalic acid and my product. Coupled with the fact that the yield was already poor, it wouldn't be worth it in my opinion.

I am atempting to make the methyl ester at the moment and will try to sulphonate it. I will also attempt the synthesis in the reference. I'll let you know how it goes.

Thanks,

Greig

[Honclbrif]

Glad I could help out. Look forward to hearing how it goes.

[Greig]

The oxidation reaction is still under reflux, however the methyl ester reaction has been "completed" and I have obtained a 107% yield...

It was a simple Fischer esterification reaction between methanol and terephthalic acid using sulphuric acid as the catalyst.

Dimethyl terephtalate, the product, is supposed to be a white solid, however what I have obtained has a crystalline sparkly orange apearance.

From my reasoning, the only way in which I can obtain a yield of over 100% is if some sulphonation has already occured in this step unintentionally.

Another idea I have which may or may not be possible is that I am wondering if carboxylic acids can form mixed anhydrides with sulphuric acids, in this case perhaps forming some oligomers due to the fact this is a dicarboxylic acid. Perhaps using 10 equivalents of H2SO4 was over the top but I added this in reference to a known procedure for a similar compound.

Has anyone Experienced a similar problem with Fischer esterification?

[Honclbrif]

Did you dry your material under vacuum? Residual moisture or solvent could easily account for a few extra %.

As for the orange: did you do an acid/base workup of your product, or did you just evaporate the solvent? the di-ester should be soluble in a solvent such as ethyl acetate and the starting acid and mono-ester byproduct should partition into saturated bicarbonate making cleanup pretty easy. Furthermore, did you perform a chromatographic separation to analyze and purify your material?

The aromatic core is very deactivated by the carboxyl groups, so I doubt that dilute H2SO4 would be sufficient for sulfonation.

[Greig]

I just dried it in the oven at 100 C over night which I expected should do the trick but perhaps not!

The NMR spectra actually shows the synthesis as relatively successful, with the main product clearly being that desired. The side products indeed appear to be the monomethyl ester and terephthalic acid at around 15% each. I will attempt the purification you suggested by partition. I have no experience with chromatography but i will try it if required.

However, the colour (at least to me) is still a mystery I think. None of the compounds I have formed should be coloured.

In other news, the oxidation of p-xylene sulphonic acid seems to have worked fantastically, with NMR showing a purity of roughly 90%, with the 10% detectable impurity being the monocarboxylic acid product. I am very inexperienced in separation, however. I presume that chromatography is the way forward here?

[Honclbrif]

Drying organics at high temp is rarely a good idea. It can lead to oxidation or other degredation pathways. The best way is usually to pull vacuum on the material and let it sit overnight. Sometimes gentle heating is required depending on the power of the vacuum and the solvent's boiling point.

Acid/base extraction will only work for removing acids or bases from non-ionizable compounds. This means you could use it to remove your di-ester (non-ionizable) from the di-acid and mono-ester (both can donate protons to form anions).

MeCO2-Ph-CO2Me + base  no reaction, soluble in organic solvent

MeCO2-Ph-CO2H + base  MeCO2-Ph-CO2^- + BH⁺, soluble in water

Same general reaction for di-acid.

You can also use this technique to separate sulfonated product from unsulfonated product, as long as the unsulfonated product is incapable of ionizing.

Another wrinkle is that your sulfonic acids (what you are ultimately trying to make) tend to be very strong acids. This will probably result in the product being very water soluble. Write out all of the possible charged states of your target compound and suspected byproducts and at what pH they should be charged or uncharged before attempting any sort of acid/base extractions. I would consult a pKa table for this.

As for cleaning up the p-xylene sulphonic acid oxidation: the reference should have described how they purified their material. I would keep following the procedure.

The orange stuff in the reaction? Who knows!? Frequently during organic reactions colored byproducts are formed. For some reason they almost always tend to be somewhere in the yellow, red, brown range. Frequently its a small amount of material with a huge extinction coefficient so a tiny bit causes a dramatic change in color. Sometimes they can be removed by extraction; activated charcoal is an older method of removing colored impurities, and chromatography can also frequently be used to remove these impurities.