[superfly]

Hi. Is there any body tried amidation reaction using -COOH and 1,2-phenylenediamine? I tried many methods, BOP; PyBOP; SOCl2; EDC; but none of these methods worked. Any suggestion for this reaction? Thanks!!

[Doc Oc]

Can you be more specific?  Solvents, temperature, time?

Peptide couplings like this can be very slow, and your aromatic diamine is going to be sluggish to react.

[superfly]

OK.
Acid is small molecule with Mt around 300-400
BOP: The BOP method is the most common for phenylenediamine. Same way as they synthesize the MGCD0103. Using DMF as solvent and add Et3N as base. Room temp, react overnight.
PyBOP: same as BOP
EDC: EDC, HOBt, DMF, rt, overnight.
SOCl2: SOCl2, then Ch2Cl2+amine+TEA.

I also tryed mono-protect of diamine. then do the coupling. But the TLC still messy and no desire product is detected in Mass Spect.

[Doc Oc]

Well, as I said, these couplings can be quite finicky.  Unfortunately, it's also difficult to monitor them by TLC when using DMF as the solvent, so that adds a degree of difficulty.  At this point, my first suggestion is to allow the reactions to go a bit longer (24 hrs or more).  Something else you can try is maybe refluxing the SOCl2 reaction to form the acid chloride, then add the diamine/Et3N later.

I can't guarantee anything, peptide couplings often cause me headaches as well, so you're not alone.

[AC Prabakar]

SOCl2: SOCl2, then Ch2Cl2+amine+TEA.
This case intresting!Because as i am running same kind of reaction.
Have you confirmed the formation of acid chloride?
What is the level of starting material?Is it present as it is or consumed?
What are the other functional groups present your statting material?
In my case i am having one amine at the other end of the starting material.As soon as acid chloride forms it reacts with internally(amine of my starting material) and given undesired product!!

[superfly]

Hi, Yes. I tried SOCl2 and I think I get the -COCl, It's very pure (Base on TLC) but I didn't confirmed it as I think it will back to -COOH once the reaction expose to water. So I run the reaction under Ar. after the starting -COOH is disapeared then I remove the solvent and add Amine in Ch2Cl2 using a needle.

After react overnight, ~70% of the amine is consumed (base on TLC). The TLC is messy and I can't even tell how many different products are there. I tried to purify one dot which can be stained in I2, but it just a undesire product.

For my starting materials...some of them contain pyrazole at the other end....some of them contain chlorobenzene. Most of them can work with con-aromatic amine~~ I just cannnot make them work with phenylenediamine....

Fustrating!! It is my last step....if I cannot complete this step, the previous work will become garbage.

[OC pro]

Fustrating!! It is my last step....if I cannot complete this step, the previous work will become garbage.

This is organic chemistry as we all love it. Keep on. There are sooo many peptide coupling reactions.
I would isolate the acid chloride like this: Evaporation of thionyl chloride (co-evaporation with dry toluene). Then you will get pure acid chloride without any thionyl chloride left which you can redissolve and treat with amine/base. We always do it like that even on a 100g scale although it is not nice to evaporate 300 ml of SOCl2.

@J-Bone: Monitoring reactions with DMF is easier than you might think. Transfer a small aliquot of the reaction mixture into a vial, dilute it with water and ethyl acetate. Then you can make a TLC of the ethyl acetate layer and DMF won´t disturb at all.

[Doc Oc]

@J-Bone: Monitoring reactions with DMF is easier than you might think. Transfer a small aliquot of the reaction mixture into a vial, dilute it with water and ethyl acetate. Then you can make a TLC of the ethyl acetate layer and DMF won´t disturb at all.

Thanks for the tip, might try that on my next peptide coupling!

[AC Prabakar]

For my starting materials...some of them contain pyrazole at the other end....some of them contain chlorobenzene. Most of them can work with con-aromatic amine~~ I just cannnot make them work with phenylenediamine....

Fustrating!! It is my last step....if I cannot complete this step, the previous work will become garbage.

Fine.now before starting the reaction carefully analyse all the  possible side products on paper.
Try to find a similar reaction(desired) on similar moiety.As u know the structure u can search for the similar structure's reactivity.
Then try it,I am sure you will get!!!!