[digchick21]

Hi i was wondering if it is possible to do ester hydrolysis and oxidation of alcohol in the same reaction flask.

[Dan]

Yes, why not?

[Archer]

Yes, if you use refluxing aqueous dichromate and sulfuric acid, however you will end up with a mixture of acids which would be difficult to separate (unless it's a lactone)

You would be better off with alkaline hydrolysis (saponification) followed by removal of the alcohol by solvent extraction or steam distillation.

[digchick21]

Thanks,
Its a lactol ester that i want to hydrolyse, then oxidise

[digchick21]

The lactol is what i want to oxidise that is

[Archer]

By lactol ester do you mean a cyclic hemiacetal which has been esterified i.e.

O=C(C)OC1CCCCO1

[Archer]

If you want to convert a lactol ester to a lactone then you will need to do this in two steps, base hydrolysis followed by non-aqueous very mild oxidation. e.g. pyridinium chlorochromate inDCM.

[digchick21]

This is what i mean...see attachment

[digchick21]

I only have a small amount of starting material (21 mg) so i want to try and minimize loss.

[Archer]

Nepeta lacol, I know it well but I only ever made it by chemical reduction of nepeta lactone.

This is an extremely sensitive molecule, you will need to proceed with extreme caution. I would hydrolyse with a suspension of K₂CO₃ in methanol. The lactol is very hard to analyse by GC you have to reduce the injector down to about 60 degees or you will destroy the molecule in the injector.

Then, probably PCC is your best bet but keep the lactone away from any bases as it hydrolyses very easily.

[Archer]

As you have so little I would do a few trial reactions in a GC sample vial with a few μg of the lactol acetate, set the injector to splitless injection so that you can monitor the reaction.

[digchick21]

How would i go about doing that, i've never done a reaction like that on such a small scale?

[Archer]

You can use a small bore hypodermic needle to collect the substrate and then wash it with methanol into a sample vial. Then you can test whether there is enough present by running a GC.

Then put a few mg of Pot. Carb. in the vial and agitate it for a few hours (or over night) then filter it through a Pasteur pipette which has been plugged with a very small quantity of cotton wool to remove insoluble material and run it again.

If it works then you can scale it up very easily. This kind of hydrolysis should be almost quantitative as the work up is filtration and removal of the solvent.

[digchick21]

Cheers, you've been a big help.

[Archer]

I would be most grateful if you could let me know how you get on.

I spent many years working with nepeta related compounds so it is an area I am still interested in even if I don't actively work with them anymore.