[kriggy]

Hey guys, Im running reaction shown in the scheme
following literature procedure from Tetrahedron Letters 54 (2013) 201–204
whis is basicaly to dissolve the starting material in trifluoroacetic acid to get 0.5M solution and then heat it at 70°C for 16 hours. My problem is that it works great for A (in the scheme) and for others, simpler diamines, while B decomposes into pretty wild mixture. I was able to indentify the product (about 30%) and some impurities: it seems that my product compound and starting material decarboxylates (is that even possible? I thought decarboxylation occurs under basic conditions at much higher temperatures) under the reaction conditions (about 50% of raections mixture) and then some intramolecular cyclization and unidentified  produts.
I tried it at lower temperatures (50, RT) and using another procedure (20% TFA in DCM at RT) today but it doesnt seem it is working (see only SM after 5hrs) so I am bit lost at the moment
Im looking for any ideas, does anyone have any useful hints? Could using trifluoroacetanhydride or trifluoracetic acid ester work?

PS: I could oxidize the methyl to carboxylic acid using KMnO4 but I would like to explore all option on cyclizing compound with COOH already present before I try to work on the oxidation

[orthoformate]

Im looking for any ideas, does anyone have any useful hints? Could using trifluoroacetanhydride or trifluoracetic acid ester work?

I feel like this is the next logical step. If this doesn't work you could protect the SM acid as methyl ester.

[kriggy]

thanks,
Did it today and It worked realy good at 0,25 mmol scale, much better than the original procedure

[NewmanProj]

Sounds like you may have been generating a benzyne via acid promoted thermal decarboxylation. This happens because your leaving group was protonated by strong acid (TFA). Very hard to prove at 70C, but nonetheless very reactive if that is what was happening.

[kamiyu]

I think based on the observation that Kriggy provided, decarboxylation happened.

The mechanism for this may be something like an intermediate acyl cation being formed due to the leaving water group, a key mechanism in the Schimdt reaction.

I am not sure if benzyne is formed because the resulting acyl cation can be trapped by the amino groups, resulting in complicated mixture. In the case of benzyne, because the solvent that Kriggy used is TFA, the results should be replacement of the original carboxylic acid with proton.

[kriggy]

Actualy the mixture was pretty complicated, I just pointed the major products that I was able to identify but there was maybe 5-7 more being present at only few % and I was unable to identify them.