[ocvihwer]

I'm converting an acid to the acetyl chloride using thionyl chloride, however, I'm having trouble tracking the reaction using TLC. The product will hydrolyze back to the starting material when I TLC it. Any good advice on how to track the reaction?

I read somewhere that you can get small aliquot of TLC sample and add ethanol or methanol to it, to convert to the ester. But wouldn't acid also do the same thing? Just slower?

[rolnor]

It will be very slow with acid so its a good way to monitor the reaction, you can use for example diethylamine also to get the amide.

[Doc Oc]

No, it wouldn't do the same thing. The acid will probably drag/streak while the ester should move fairly easily (depends on what's in the rest of the molecule).

[wildfyr]

@Rolnar, I think the acid to acid chloride is faster than alcohol to alkyl halide.

OP, This is a case where you should just do it at reflux overnight and trust it. Thionyl chloride is a champ, these reactions are usually quantitative. If you want to give it a boost add a drop of DMF, its a catalyst for this reaction. Also, its very common to use thionyl chloride as the solvent for this reaction, so you get a huge excess fighting for you too.

If its not complete, whatever you do the next step (amine? alcohol?), it should be easy to use acid/base extraction to get any carboxylic acid that didnt make it

The alcohol trick might work though, just take a bit and put it in dry methanol. The acid chloride will esterify WAY faster than the ester under ambient conditions. Like... months faster. Ive never tried it for checking by TLC.

[AWK]

I Any good advice on how to track the reaction?

¹H NMR

[Babcock_Hall]

AWK,

Can you explain how to use H-1 NMR efficiently to track a reaction?  Solvent would have to be removed almost completely, I would think.  Anything else?

[AWK]

Acetic acid, acetic anhydride and acetyl chloride show sharp proton signals below 2 ppm, above 2 ppm and close to 3 ppm, respectively. They are miscible with CCl₄. After evolution of SO₂ and HCl, a small sample of the  reaction mixture can be diluted with CCl₄ and measured (with addition of CDCl₃ or external TMS) for determination of these compounds (if present in reaction mixture).

[wildfyr]

AWK,
I don't think ocviher is actually making acetyl chloride from acetic acid (CH3COCl), I think he is just describing the functional group on a larger  molecule. One could use carbon NMR to distinguish between the two functional groups, but again, getting an aliquot in to a tube while keeping everything bone dry during the NMR seems like a lot of trouble for a reaction that typically works perfectly overnight at reflux. I think the esterification trick on TLC is at least easy enough to try if you really really want to track conversion.

Hey ocviher, another trick occurs to me that might work better. Try quenching your reaction in an aprotic solvent like DCM that is spiked with a bit of an amine like aniline or butylamine. This would give you an amide frpm the acid chloride, and leave the carboxylic acid alone. It also should outcompete any ambient water which would give you a more accurate picture of conversation. If you use aniline remember that it shows up on TLC too, so run aniline alongside the TLC so you dont get confused between your aryl amide product and aniline.

[AWK]

Rolnor in the second post suggested diethylamine, rather without acceptance. Any method except crazy TLC of acyl (or acetyl) chloride would be better.

[SynDude]

I would not use TLC for monitoring such a reaction since acids tend to stick to the baseline and therefore cannot be seen separately from other polar impurities. I'd go for 1H-NMR or HPLC-MS (after a MeOH quench)

[kriggy]

Depending on structure but I do TLC of carboxylici acids with EtOAc:Hexane mixture rather easily. It all depends on the structure of compound