[aalexopo4990]

I am trying to couple a carboxylic acid (4-diphenylphosphino benzoic acid...basically triphenylphosphine with a single ortho carboxylic acid) to the side chain of a lysine in my peptide. The procedure I am following uses EDC and HOBt in DMF with no mention of pH or any base added. My question is:
Is the pH of the reaction important? At first glance it would seem to me that the lysine must not be protonated in order for it to act as a nucleophile and attack the activated ester, but I might be missing something especially because I am not sure how pH relates to aprotic solvents.
ALSO: I have the same question when using DMSO as a solvent. I might need to switch to DMSO as DMF damages the filter/dialysis work up.

Reference: Allylic Substitution in Water Catalyzed by Amphiphilic Resin-Supported Palladium-Phosphine Complexes. Uozumi, Y. Tettrahedron 1999. Uozumi has more papers using the same procedure with both solid state and solution phase chemistry.

Thank you in advance for your responses. I will try to update this post as much as possible.

[pgk]

Indeed, acid and base strength varies within different solvents. But, the term pH is applied on aqueous solution or aqueous solvent mixtures, only. However and in terms of reaction mechanism, direct amidation is a dehydration reaction and therefore, aqueous medium and buffers must be avoided. Besides and in absence of catalyst, direct amidation occurs via the preliminary formation of the amine carboxylate salt, followed by thermal dehydration.
Switching DMF by DMSO, mainly depends on the reactants solubility and must be verified in practice. Remember that you don’t have a simple carboxylic acid but a phosphinebenzoic one.
Please, take a look to the attached .PDF-file that might be helpful.

[pgk]

Sorry, I forgot to attach the .PDF-file. Here it is.

[aalexopo4990]

So as of now, the reaction appears to be working in both DMF and DMSO with no base added - on the basis of a negative kaiser test (ninhydrin stain comes up with no purple/pink color).
The ninhydrin is only a qualitative test I cannot comment on yield as of this moment but things are looking good.

[pgk]

Thanks for the updating.