[uglepik]

When coupling an alcohol and an amine using carbonyldiimidazole (to obtain a carbamate link), is it neccesary to add a base for the reaction between the CDI-activated imidazolide of the alcohol and the (primary) amine? Or is it sufficient that the imidazole leaving-group removes the proton from the amine?

Best regards,
Andreas

[tingfeng]

I think it is not necessary to add another base.

[Doc Oc]

Yes, add base (triethylamine is fine in this case).  It is easily removed in the work-up.

[uglepik]

Yes, add base (triethylamine is fine in this case).  It is easily removed in the work-up.

What would be the rationale for adding a base? To ensure complete deprotonation of the amine? Do you have any thoughts on whether base would speed up or slow down the reaction?

[Doc Oc]

Yes, it is to scavenge acidic protons from the reaction.  I haven't measured the reaction kinetics with or without base, so I don't know if it speeds up or slows down the reaction.

[uglepik]

Yes, it is to scavenge acidic protons from the reaction.  I haven't measured the reaction kinetics with or without base, so I don't know if it speeds up or slows down the reaction.

The trick about this reaction is that the imidazole leaving group takes the proton from the amine. Therefore a base is not necessarily required (I would assume). As I would guess that the imidazole actually NEEDS a proton to act as leaving group, it might be that base interferes with this proton transfer and thus slows down the reaction... But this is speculation of course.

[tingfeng]

I performed this reaction before. CDI was added to the solution of acid. after the the acid was consumed amine was added. I think whether add base or not or not it is depend on your substrate.