Derivatization of Glycols

[Christsean]

Does anyone know of a good method for derivatizing glycols? (triethylene glycol, dipropylene glycol, and propylene glycol) My research has shown p-toluenesulfonyl isocyanate to be a good derivatizing reagent, but I'm not sure in what quantities and with what other reagents.

[Vlad Orlovsky]

Sean you might want to consider something smaller (acetic anhydride?). You don't want to create molecules which are too hydrophobic

[Christsean]

Hey Vlad, I have been looking at a derivatization procedure using Benzoyl Chloride that takes roughly one hour to process before you can begin to test. I need something a bit faster to keep up with the production demands.

I have been unable to find a method using phenyl isocyanate.

Do you think that acetic anhydride would be my best route? I am not very familiar with the chemistry behind what make a good derivitizing agent or not for my application.

[Vlad Orlovsky]

With any derivatization you need to look at conversion rate and time. With pheyl isocyanate reaction is usually done in 15 minutes, you will need to use excess of isocyanyte and then "quench" sample with methanol. If you reaction is not completed you end up with partially derivatized glycols. So if you have even two glycols you might end up having 4 products, plus quenched PIC. With acetyl chloride is the same story., but it is cheaper. I don't know how often people use derivatization method in production.

[mardexis]

Do you not have access to a GC? That would beat the heck out of any derivatization.

[Christsean]

Yes. I am using the Stabilwax column. It works great. I just wanted to see if it was possible to test all three on the same column with little effort.

[chromatographer1]

I have used acetic anhydride with a pyridine catalyst reaction and pentane solvent with NaCl (aq) conc extraction to derivitize samples for QA analysis. It takes about 10 to 12 min per sample but several samples can be acetylated at the same time and kept in a freezer until ready for injection. The organic layer sits atop the aqueous salt solution so it is easy to sample. An internal standard is also recommended due to possible handling losses.

I did QA for manufacturing with derivitizations for years. It can be routine. A few hours of validation might be required.

best wishes,

Rodney George

[Christsean]

Do you remember the exact steps and concentrations of each reagent?

[chromatographer1]

There are books about derivitization methods available. I would suggest you use a documented procedure and not my memory.

I do remember I created a method from scratch after reviewing the literature and it worked well.

The pyridine was 1/10 of the acetic anhydride (50-100µL to about 0.5 to 1mL) in volume for 25mg of glycol or alcohol. The non-polar extraction volume was about 1mL and 7mL of aqueous salt. I may have added a small amount of methylene chloride to the hexane for some extractions.
I heated the reaction solution for 10-15 min at 110°C before cooling to ambient and quickly carefully briefly opening the reaction vial to add the non-polar solvent which was added and shaken before the salt water.

Oh the 1970s and 80s were good years !

best wishes,

Rodney George
consultant

[Christsean]

That's a pretty good memory! I am currently searching for a good book about derivatizations. If you or anyone else has a good suggestion, I would be most appreciative.

[Christsean]

With any derivatization you need to look at conversion rate and time. With pheyl isocyanate reaction is usually done in 15 minutes, you will need to use excess of isocyanyte and then "quench" sample with methanol. If you reaction is not completed you end up with partially derivatized glycols. So if you have even two glycols you might end up having 4 products, plus quenched PIC. With acetyl chloride is the same story., but it is cheaper. I don't know how often people use derivatization method in production.

Vlad, will I need to use DMF for this reaction or can I use just phenyl isocyanate and methanol?

[Consumer Products Guy]

I have been unable to find a method using phenyl isocyanate.

We've used this for fatty alcohol type materials.

1. Transfer 1 drop of sample into a screw-top cone-bottom autosampler vial (melt and mix solid samples first, if possible).

2. Using an Eppendorf-type pipet, add 10 ul phenylisocyanate. Cap the vial, and heat for 15.0 minutes at 60 *C.

3. Cool to room temperature, then add 1.0 ml methanol. Cap and mix well. assay on RP-18 column, detection about 280nm.

L. Nitschke and L. Huber, “Analysis of ethoxylated alcohol surfactants in water by HPLCâ€

[Christsean]

Thank you CPG.

[chromatographer1]

Wiley

[Christsean]

Thanks C1!