[_Espard_]

I am interested if there is any way to selectively promote aminolysis (by an amine) to a substrate in alkaline solution without hydrolysis caused via (-)OH competing/overpowering.

I ended up coming across information for peptide(ish) coupling reactions, but found that they were limited to the neutral pH region mostly as there was nothing for alkaline conditions.

Anybody have any clue or idea how such a reaction would take place (i.e. what substrates)? Not sure if my question is clear enough, can explain more if need be!

[Dan]

You can't stop competition, you can only reduce the amount of ^-OH present. The usual strategy is to use a minimum amount of water - so using conc. aqueous ammonia in an alcoholic solvent, or even using ammonia in an anhydrous solvent by saturating the solvent of choice with gaseous ammonia (anhydrous ammonia solutions are also commercially available).

Unless you are operating at very high pH, ammonia will normally outcompete hydroxide anyway. Consider conc. ammonia and the relative pKas of ammonium and water - there is far more ammonia present than hydroxide. I've adapted a few literature preparations that originally called for gaseous or anhydrous ammonia by using conc. aqueous ammonia instead and they worked perfectly well.

[_Espard_]

Thanks for the input, and I totally get what you are saying.

I have necessity to employ this in an aqueous system - is this pretty much futile? Is there any sort of compound/metal ion that has a naturally high affinity for nitrogen nucleophiles over oxygen nucleophiles and may be adaptable for alkaline aqueous systems?

[Dan]

I have necessity to employ this in an aqueous system - is this pretty much futile? Is there any sort of compound/metal ion that has a naturally high affinity for nitrogen nucleophiles over oxygen nucleophiles and may be adaptable for alkaline aqueous systems?

Give it a shot and see what happens. What exactly are you trying to do?